Biological processes with circadian rhythms show periodicity that correlates with the day/night cycle, and many metabolic pathways display such a regulatory mechanism. Prior work has suggested that between 2 and 10% of the liver transcriptome is under circadian control. Gatfield et al. show that miR-122, an abundant hepatocyte microRNA, is under circadian control. The abundance of the miR-122 precursor varies 4- to 10-fold during the day. However, accumulation is constant in the liver of mice lacking the orphan nuclear receptor REV-ERBα. When miR-122 is knocked down, hundreds of mRNAs are expressed. Peroxisome proliferation–activated receptor (PPAR) β/δ and the coactivator SMARCD1/BAF60a, two known metabolism regulators, are specific miR-122 targets, linking circadian rhythms with the PPAR family of nuclear receptors and liver metabolism.